Title:Molecular Bases of Chemoresistance in Cholangiocarcinoma
Volume: 18
Issue: 8
Author(s): Jose J.G. Marin*, Elisa Lozano, Oscar Briz, Ruba Al-Abdulla, Maria A. Serrano and Rocio I.R. Macias
Affiliation:
- Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca,Spain
Keywords:
Chemotherapy, drug metabolism, drug transport, liver cancer, pharmacology, treatment, tumor.
Abstract: The multidrug resistance (MDR) phenotype accounts for the poor response of cholangiocarcinoma
to available antitumor drugs. This is an important limitation to the use of pharmacological
approaches, both as adjuvant therapies and for treating advanced CCA when surgical removal is
not possible. MDR is the result of a complex combination of defense mechanisms against toxic
compounds already present in cholangiocytes, which play a role in the physiology of these cells by
protecting the biliary epithelium from the toxins reaching the biliary tree with the blood that perfuses
this tissue, or that are secreted by hepatocytes into bile, to which cholangiocytes are exposed.
These mechanisms of chemoresistance (MOC) are also present, usually with enhanced efficacy, in
tumors derived from cholangiolar cells. The present review article is an update of the state-of-the-art
regarding the MOC involved in the poor response of CCA to antitumor drugs. These MOC have
been classified as: changes in the amount of drug in the cells due to decreased uptake (MOC-1a) or
enhanced efflux (MOC-1b); altered proportions between prodrug, active drug and inactive metabolites
(MOC-2); changes in the molecular targets of antitumor drugs (MOC-3); an enhanced ability
of tumor cells to repair drug-induced DNA damage (MOC-4), and an impaired apoptosis/survival
balance (MOC-5).
